Trypanosoma cruzi is the aetiological agent of Chagas' disease, an important cause of chronic cardiomyopathy. We previously demonstrated a role for endothelin-1 (ET-1) in the pathogenesis of chagasic heart disease. In order to explore further the significance of ET-1 in chagasic heart disease, we infected ET-1 (flox/flox); α-MHC-Cre(+) (ET-1KO) mice, in which the ET-1 gene has been deleted from cardiac myocytes, with 104T. cruzi (Brazil strain) trypomastigotes. As controls, we used ET-1 (flox/flox);Cre(-) (FLOX) and C57BL/6×129sv (WT) mice. All mice survived and were evaluated 150–160 days post-infection. Cardiac magnetic resonance imaging revealed a significant increase in right ventricular internal diameter in all infected animals except ET-1KO mice (control WT, 1.6±0.10mm; infected WT, 2.8±0.15mm; control FLOX, 2.04±0.02mm; infected FLOX, 2.76±0.28mm). There was no significant difference in right ventricular internal diameter between infected and uninfected ET-1KO mice (control ET-1KO, 1.83±0.11mm; infected ET-1KO, 2.14±0.20mm). In another series of experiments, transthoracic echocardiography was performed on uninfected as well as infected ET-1KO mice, and uninfected and infected FLOX mice. Both infected groups had an increased left ventricular end-diastolic diameter and reduced fractional shortening. In addition, relative wall thickness was also decreased in infected animals. However, the magnitude of these changes was less in infected ET-1KO mice. These data provide further support for a role for ET-1 in the pathogenesis of chronic chagasic heart disease, and indicate that cardiac myocytes are an important source of ET-1 in this disease.
Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: molecular genetic evidence
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Huan HUANG, Masashi YANAGISAWA, Yaz Y. KISANUKI, Linda A. JELICKS, Madhulika CHANDRA, Stephen M. FACTOR, Murray WITTNER, Louis M. WEISS, Richard G. PESTELL, Vitaliy SHTUTIN, Jamshid SHIRANI, Herbert B. TANOWITZ; Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: molecular genetic evidence. Clin Sci (Lond) 1 September 2002; 103 (s2002): 263S–266S. doi: https://doi.org/10.1042/CS103S263S
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